1. The value of male HPV vaccination in preventing cervical cancer and genital warts in a low resource setting Monisha Sharma, Stephen Sy, Jane J. Kim Center for Health Decision Science Harvard T.H. Chan School of Public Health

2. We will discuss this paper at #BlueJC on Twitter and Facebook. Join us!TwitterFacebook How does #BlueJC work? – Leung E, Tirlapur S, Siassakos D, Khan K. BJOG. 2013 May;120(6):657-60. http://bit.ly/10VaiRZhttp://bit.ly/10VaiRZ For further information: – Follow @BlueJCHost@BlueJCHost – Go to http://bluejournalclub.wordpress.com/http://bluejournalclub.wordpress.com/ – See BJOG Journal Club section at http://www.bjog.org/ http://www.bjog.org/

3. Scenario At a conference on cervical cancer prevention, a speaker presented data on the cost-effectiveness of HPV vaccination for girls in Thailand (see BJOG. 2012;119(2):166-76). An audience asked, “Would vaccinating both boys and girls be better than vaccinating girls only?”.

4. Background Cervical cancer (CC) leads to significant mortality and morbidity in low, middle-income countries (LMICs) In LMICs, CC screening coverage is low and of variable quality due to the lack of resources and infrastructure HPV vaccination has shown promise as a primary prevention strategy to reduce CC The cost-effectiveness and appropriate target population of HPV vaccination in LMICs are to be elucidated South Vietnam has high CC incidence (26/100,000 person- years) and low (<5%) CC screening coverage

5. Background What is the incidence of cervical cancer in your country? What are the uptake rates of cervical screening and HPV vaccine in your country? What is GAVI Alliance? How does it achieve its goals? (http://www.gavi.org/about/)

6. In LMICs, is HPV vaccination of both girls and boys cost-effective compared to vaccinating girls only? The Research Question

7. Description of Research (PICOD) ParticipantsMale and female population (≥ 9 years old) in South Vietnam InterventionHPV vaccination for both male and female ComparisonHPV vaccination for female only OutcomesEconomical costs, estimates of cervical cancer and genital warts incidence, mortality and quality-adjusted life years (QALYS) Study DesignEconomic evaluation using mathematical models

8. Methods Mathematical models were used to – Simulate the dynamic transmission of HPV infection – Estimate cervical cancer and genital warts cases – Estimate costs associated with different scenarios of HPV vaccination and cervical screening coverage Models were calibrated to epidemiologic data from South Vietnam at different HPV vaccine costs and cervical cancer screening coverage rates Main outcome measures: incremental cost-effectiveness ratios (ICERs), i.e. cost per quality-adjusted life year (QALY) gained

9. Overview: Mathematical Models

10. Methods What are the advantages and disadvantages of using a mathematical model to address this research question? What are the alternative approaches to answer this research question? Critically appraise this study using the CASP checklist for economical evaluation:http://bit.ly/1EX0KXEhttp://bit.ly/1EX0KXE

11. Incremental cost-effectiveness ratios by cost per vaccinated adolescent and vaccination coverage* *Outcomes: CC and genital warts. Bolded: scenarios where HPV vac of boys is <Vietnam’s GDP per capita (I$2,800); shaded: strategies where HPV vac of boys <50% Vietnam’s GDP per capita; “CS”: strategies that were cost-saving compared to no intervention. Natural history: No CC screening or HPV vaccination. Mean cancer reduction: Compared to natural history Cost per vaccinated individual Mean cancer reduction I$10I$25I$50I$75 (I$2 per dose)(I$5 per dose)(I$10 per dose)(I$15 per dose) 25% Coverage Natural history------------- Vaccination, girls only20.0%CS $211$454 Vaccination, girls and boys22.7%$49$572$1,445$2,317 75% Coverage Natural history------------- Vaccination, girls only50.2%CS $252$515 Vaccination, girls and boys52.9%$280$1,153$2,608$4,062 90% Coverage Natural history------------- Vaccination, girls only56.9%CS $253$517 Vaccination, girls and boys58.2%$519$1,751$3,806$5,860

12. Sensitivity analysis for ICERs for vaccinating girls and boys (at I$5/dose) Impact of varying assumptions on ICERs of vaccinating girls and boys vs. vaccinating girls alone in South Vietnam at different coverage levels for vaccine costs of I$5 per vaccinated adolescent. Red dashed lines: ICER threshold of Vietnam’s GDP per capita. Black dashed lines: 50% of Vietnam’s GDP per capita.

13. Using this study as an example, explain what is incremental cost-effectiveness ratio (ICER). What is the purpose of sensitivity analysis in economical evaluations? What is your interpretation of the results presented? Results

14. Vaccination of boys would yield an additional of ≤3.6% absolute cervical cancer risk reduction, compared to vaccinating girls alone HPV vaccination of boys at I$10/dose was cost-effective at or below 75% screening coverage using a threshold of Vietnam’s GDP per capita (I$2,800). At a lower threshold of 50% of Vietnam’s GDP (I$1,400), vaccinating boys was not cost-effective at >I$5/dose. Results were robust to sensitivity analyses. Authors’ summary of results

15. Where may the results of this study be generalisable? What may influence how policy makers utilise findings of economical evaluations? How can researchers maximise the potential of their research being utilised for health policy decision- making? Should we give HPV vaccines to all boys in LMICs? Discussion

16. HPV vaccination of boys provides some benefit over vaccinating girls only to reduce cervical cancer and genital warts. HPV vaccination of boys may be cost-effective at low vaccine costs Strategies focusing on achieving high HPV vaccine coverage for girls may be more efficient in low resource settings Authors’ conclusions

17. This analysis only considered health benefits from prevention of CC and genital warts. We did not consider other HPV-related cancers including oropharyngeal, anal, penile, vaginal, and vulvar cancer. What effect would the inclusion of these cancers have on the ICERs for vaccinating boys and girls? Limitations of this study

18. Suggested reading Cohen DJ, Reynolds MR. Interpreting the results of cost-effectiveness studies. J Am Coll Cardiol. 2008 Dec 16;52(25):2119-26. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, Augustovski F, Briggs AH, Mauskopf J, Loder E; CHEERS Task Force. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. BMJ. 2013 Mar 25;346:f1049. Gold M. Pathways to the use of health services research in policy. Health Serv Res. 2009 Aug;44(4):1111-36. Haynes AS, Gillespie JA, Derrick GE, Hall WD, Redman S, Chapman S, Sturk H. Galvanizers, guides, champions, and shields: the many ways that policymakers use public health researchers. Milbank Q. 2011 Dec;89(4):564-98. Linhares IM, Witkin SS. HPV vaccination: unanswered questions remain. BJOG. 2015 Jan;122(1):118. Sharma M, Ortendahl J, van der Ham E, Sy S, Kim JJ. Cost-effectiveness of human papillomavirus vaccination and cervical cancer screening in Thailand. BJOG. 2012 Jan;119(2):166-76.

19. Monisha Sharma University of Washington, Department of Epidemiology, 1959 NE Pacific Street, Seattle, WA 98195, USA; msharma04@gmail.com msharma04@gmail.com Stephen Sy and Jane J. Kim Department of Health Policy and Management, Center for Health Decision Science, Harvard T.H. Chan School of Public Health, 718 Huntington Avenue, 2 nd Floor, Boston, MA 02115, USA MS, JJK and SY have no conflicts to declare. Authors’ affiliations

20. The authors would like to acknowledge the contributions of the cervical cancer prevention team at the Center for Health Decision Science at the Harvard T.H. Chan School of Public Health. This study was funded by the Bill & Melinda Gates Foundation (30505). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the article. Acknowledgement